Menu

Close

GSK3 Controls Migration of the Neural Crest Lineage

Sandra G Gonzalez Malagon, Anna Lopez Munoz, Daniel Doro, Triona Bolger, Evan Poon, Elizabeth Tucker, Hadeel Adel Al-Lami, Matthias Krause, Christopher Phiel, Louis Chesler, Karen J Liu

Preprint posted on May 01, 2018 http://dx.doi.org/10.1101/243170

ALK-mediated GSK3 phosphorylation is a conserved mechanism that regulates neural crest migration in development and a possible key to aberrant migration in neuoroblastoma.

Selected by Amanda Haage

Categories: cell biology, neuroscience

Why This Is Cool –Neural crest migration is critical for proper development, but aberrant migration of these cells can also contribute to many cancers, such as neuroblastoma. Despite the obvious importance, mechanisms underlying neural crest migration are relatively unknown due to the technical difficulty of studying these cells in vivo. Through the use of an ex vivo culture system, as well as both genetic and pharmalogical inhibition, the authors show a novel requirement of GSK3 tyrosine phosphorylation (pY-GSK3) for proper neural crest migration. They demonstrate the requirement for pY-GSK3 across two different species (mouse and frog), providing excellent support for the argument of a conserved and general regulatory mechanism. They go on to show that loss of GSK3 results in specific defects to the cytoskeleton, mainly changes to the stability and localization of known players (actin, microtubules, FAK, Rac1, cdc42). This demonstrates how the migration machinery may be regulated by pY-GSK3. They then investigate the upstream effectors, focusing on ALK because of its known association with neuroblastoma. ALK is shown to be in the right place at the right time and loss of ALK phenocopies loss of pY-GSK3 in the neural crest. Lastly, they end with drawing similar conclusions in neuroblastoma cell lines, demonstrating how this general mechanism for regulating neural crest cell migration could become deregulated in neural crest derived cancers.

Why I Selected It –  I’m specifically interested in using the ex vivo culture system of neural plates, described here, for my own work. They have presented an excellent characterization of the migration and polarity of the mammalian neural crest, a difficult to isolate primary cell population.

Fig 1 – (I) Transverse cranial section of E9 mouse showing immunoflourescent staining for Hoechst/DNA (blue), pY-GSK3 (green) and p75NTR (neural crest, red). (J) Schematic of E8.5 mouse embryo depicting cranial neural crest (CNC) dissection.

 

Open Questions – 

  • How does GSK3 exert effects on FAK and the cytoskeleton? Is it known to bind directly to any of these players? What could mediate this interaction and the outcomes presented here?
  • Are similar mechanisms required in other neural crest populations? Here they focus on the outcomes for craniofacial development, but what about melanocytes or cardiac neural crest cells?

Related Research- 

  • Direct previous study by this group
    • Liu, K. J., Arron, J. R., Stankunas, K., Crabtree, G. R. & Longaker, M. T. Chemical rescue of clef palate and midline defects in conditional GSK-3beta mice. Nature 446, 79–82, https://doi.org/10.1038/nature05557 (2007).
  • GSK3 & cell migration
  • ALK & neuroblastoma

 

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    Spatiotemporally controlled Myosin relocalization and internal pressure cause biased cortical extension to generate sibling cell size asymmetry

    Tri Thanh Pham, Arnaud Monnard, Jonne Helenius, et al.



    Selected by Giuliana Clemente

    Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading

    Hamish T J Gilbert, Venkatesh Mallikarjun, Oana Dobre, et al.



    Selected by Rebecca Quelch

    1

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Clathrin plaques form mechanotransducing platforms

    Agathe Franck, Jeanne Laine, Gilles Moulay, et al.



    Selected by Amanda Haage

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    A non-cell autonomous actin redistribution enables isotropic retinal growth

    Marija Matejcic, Guillaume Salbreux, Caren Norden



    Selected by Yara E. Sánchez Corrales

    1

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Arnaud Monnard

    1

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

    Pierre ROME, Hiroyuki OHKURA



    Selected by Binyam Mogessie

    ERM proteins: The missing actin linkers in clathrin-mediated endocytosis

    Audun Sverre Kvalvaag, Kay Oliver Schink, Andreas Brech, et al.



    Selected by Nicola Stevenson

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

    Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, et al.



    Selected by Penelope La-Borde

    Atomic model of microtubule-bound tau

    Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, et al.



    Selected by Satish Bodakuntla

    1

    Close

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.

    Accept